Epidemiology of Clinical Malaria in Western Kenya Highlands Malaria is a major public health problem in Africa. An estimated one million people in Africa die from malaria each year, with the majority of fatalities occurring in children under the age of 5 in areas south of the Sahara. The African highlands (areas with elevation above 1500 m above sea level), where malaria used to be absent or very limited, has experienced periodic epidemics since the 1980's, with more than 110,000 fatalities each year. With the support of Global Funds to Fight Malaria, Presidential Malaria Initiatives and other private foundations, intensive control efforts were initiated in 2006 in Kenya. These efforts included large-scale distribution of insecticide treated nets, indoor residual spraying, and the use of artemisinin- based combination therapy (ACT) to treat uncomplicated malaria. Although these control measures appear successful in reducing malaria prevalence and incidence, there is no rigorous monitoring and evaluation program for these efforts because data on malaria prevalence and incidence are often difficult or too expensive to obtain on a large geographic scale. While hospital-based data is available, and an inexpensive source of data, there is uncertainty about the reliability of this data source. Additionally, clinical malaria incidence in the highland regions of western Kenya remains so high that intensive vector control measures and new antimalarial treatment regimes are being implemented. The objectives of this application are to determine the reliability of hospital-based malaria case data for representing natural malaria incidence and for the usefulness of this data in impact evaluation of malaria control measures, and to determine the risk factors for clinical malaria infection in areas undergoing intensive malaria intervention. I have designed two specific aims. The first specific aim tests the hypothesis that misdiagnosis, home treatment and hospital treatment-seeking behaviour are the major sources of errors in hospital-based malaria case data for representing natural malaria incidence rates. The second specific aim tests the hypothesis that clinical malaria infection risk in individual households may be affected by biotic and abiotic factors, and socioeconomic matters, and the importance of the risk factors for clinical malaria may be determined by using case-control studies. This research will answer important questions such as whether hospital-based malaria case data are suitable for malaria incidence monitoring and impact evaluation of malaria control efforts, and will help to develop new methods that target the important risk factors for clinical malaria in the era of intensive malaria control in Africa. PUBLIC HEALTH RELEVANCE: Epidemic malaria in the African highlands kills about 110,000 people each year and 110 million people are at risk of malaria infection. Understanding the risk factors for clinical malaria infection in the highlands will help to develop cost-effective interventions to combat malaria epidemics. The accuracy and sensitivity of hospital-based clinical malaria data is essential to measure the impact of malaria interventions.